L-acetylcarnitine

From Synergy TimesTAKE-HOME MESSAGEL-acetylcarnitine (LAC) may be useful in the treatment of various neuropsychiatric symptoms and syndromes, ranging from depression to Alzheimer's disease. A reasonably solid body of evidence supports the use of LAC in patients with pain syndromes, including painful neuropathy of diabetic and other etiology. LAC is probably ineffective in pediatric ADHD. Effective doses for various indications have generally been in the 1-4 g/day range, and treatment durations have commonly extended for months to a year. LAC appears to be well tolerated.

========================

THE SYNERGY TIMES

========================Mar 23, 2013; Vol 13 No 32L-ACETYLCARNITINE IN NEUROPSYCHIATRYOver the years, a modest body of evidence has accumulated to suggest that the dietary supplement L-acetylcarnitine (LAC) has therapeutic properties in neuropsychiatric patients. A brief overview of the literature is provided below.

Antidepressant action of L-acetylcarnitine in animal modelsLAC has antidepressant effects in rats with genetically programmed depression as well as in mice with stress-driven depression. The antidepressant benefits appear within 3 days of treatment; in contrast, benefits with clomipramine appear only after 2 weeks. Additionally, LAC-induced antidepressant benefits persist for 2 weeks after drug discontinuation (Nasca et al, 2013).

L-acetylcarnitine and depression1. In a large (n=204), 12-week RCT, LAC (1 g/day) was as effective an antidepressant as amisulpride (50 mg/day) in patients with dysthymia (Zanardi and Smeraldi, 2006).

2. In a 7-week RCT in 80 elderly patients with dysthymia, LAC (3 g/day) and fluoxetine (20 mg/day) were associated with similar outcomes except in that the onset of antidepressant action was at week 1 with LAC as compared with week 2 with fluoxetine.

L-acetylcarnitine and other neuropsychiatric symptoms and syndromes1. In a self-controlled study with a placebo lead-in phase, LAC (1.5 g/day) improved memory, general cognition, and mood in elderly subjects (Salvioli and Neri, 1994). A meta-analysis of RCTs in Alzheimer's disease found that LAC was superior to placebo with small effect sizes for an integrated summary effect (ES=0.20; 95% CI, 0.11-0.30) and for global change (ES, 0.32; 95% CI, 0.18-0.47).

3. In a large (n=102), 10-week RCT, LAC (1.5 g/day) was superior to placebo in reducing pain and depression associated with fibromyalgia (Rossini et al, 2007).

4. A small (n=40), 6-week RCT found that LAC (500-1500 mg/day) was no better than placebo in children and adolescents with ADHD who were already receiving methylphenidate (20-30 mg/day) (Abbasi et al, 2011). Whereas one previous 1-year RCT (n=63) found that LAC reduced hyperactivity in fragile X boys with ADHD (Torrioli et al, 2008), another 16-week RCT (n=112) found that LAC was ineffective in ADHD children (Arnold et al, 2007).

5. Intravenous LAC (1-3 g/day for 10 days) rapidly reduced anhedonia and melancholia scores in a placebo-controlled trial in64 anhedonic alcoholic patients who had undergone detoxification (Martinotti et al, 2011). In the same study, oral LAC was continued to a 90-day endpoint. LAC reduced craving and increased time to the first drink (Martinotti et al, 2010).

Mechanism of action1. If LAC does have antidepressant action, what might be the mechanism? Nasca et al (2013) suggested that LAC acts epigenetically, through acetylation of histone proteins that regulate the transcription of BDNF and mGlu2 metabotropic glutamatergic receptors in the hippocampus and prefrontal cortex. They showed that the antidepressant action of LAC was diminished or abolished in mGlu2 knockout mice, and in animals treated with a mGlu2/3 antagonist.

2. LAC has many effects in mice: noradrenaline is increased and GABA is decreased in the hippocampus, and serotonin is increased in the cerebral cortex (Smeland et al, 2012).

ConclusionsL-acetylcarnitine (LAC) may be useful in the treatment of various neuropsychiatric symptoms and syndromes, ranging from depression to Alzheimer's disease. A reasonably solid body of evidence supports the use of LAC in patients with pain syndromes, including painful neuropathy of diabetic and other etiology. LAC is probably ineffective in pediatric ADHD. Effective doses for various indications have generally been in the 1-4 g/day range, and treatment durations have commonly extended for months to a year. LAC appears to be well tolerated.

Comments1. Most of the literature on LAC has emerged from Italy.

2. There is no patent in force on LAC, and it is therefore unlikely that LAC will be seriously investigated as a prescription medicine. This is unfortunate, because it means that there is little hope for serious research on the drug.

===============================================THE SYNERGY TIMES is a regular e-newsletter which provides a capsule of information on mental health and allied sciences. While effort is made to provide accurate reviews, the onus of responsibility in the use of information lies with the reader. To subscribe to, unsubscribe from, or receive back issues of THE SYNERGY TIMES, please e-mail Dr. Chittaranjan Andrade (andradec@gmail.com).

The contents of THE SYNERGY TIMES are copyright. No part of THE SYNERGY TIMES may be reproduced without the written consent of the copyright holder (Chittaranjan Andrade, M.D.; andradec@gmail.com).

Thank you for reading THE SYNERGY TIMES. This newsletter generates a substantial, unrestricted, annual grant from the Synergy Division of Sun Pharmaceutical Industries Limited, Bombay, to registered, nongovernmental organizations which educate underprivileged children in urban and rural Karnataka. This newsletter also receives a generous, unrestricted grant from the British Association for Psychopharmacology, U.K., for the treatment of visual disturbances in the underprivileged at a general hospital in Bangalore.